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Annals of Oncology
patients who did not receive anti-EGFR therapy and had K-RAS status ascertained,
patients with K-RAS-wt patients had better survival outcomes compared to
K-RAS-mt patients. In the adjuvant setting (Disease Free Survival HR 0.75 95% CI:
0.66-0.87, p < 0.001), 1 st line metastatic (Overall Survival: HR 0.85 (95% CI:
0.76-0.96), p < 0.01) and refractory disease (Overall Survival: HR 0.75 95% CI:
0.64-0.89, p < 0.01).
Conclusion: Beyond being a predictive marker of non-response to EGFR antibodies,
among patients with early stage, 1 st line metastatic and refractory colorectal cancer
who do not receive anti-EGFR therapy, K-RAS is a negative prognostic marker.
Disclosure: All authors have declared no conflicts of interest.
534P PROGNOSTIC IMPACT OF PHOSPHO-ER-ALPHA (PER-α) IN
SURGICALLY RESECTED COLON CANCER
I. López Calderero 1 , A.C. Moya 2 , A.A. Gonzalez 3 , A.C. Carranza 4 , M.C. Conde 1 ,
S. Molina-Pinelo 2 , M.D.P. Herrera 2 , M.L.L. Miron 1 , P.E. Garcia 1 ,
R. Garcia-Carbonero 1
1 Oncology Service, Hospital Virgen del Rocio, Seville, SPAIN, 2 Laboratorio de
Biologia Molecular del Cancer, Instituto de Biomedicina de Sevilla, Seville,
SPAIN, 3 Departamento de Anatomía Patológica, Hospital central de Asturias,
Oviedo, SPAIN, 4 Pathology Department, Hospitales Universitarios Virgen del
Rocio, Seville, SPAIN
Background: Preclinical models and randomized clinical trials suggest a protective
role for estrogens against colorectal cancer (CRC). ER-β is the prevalent estrogen
receptor in normal colonic mucosa, while its expression is significantly reduced in
CRC. An increased ER-α/β ratio has been documented in colon carcinomas and this
is associated with increased proliferation and decreased apoptosis. The aim of our
study was to evaluate the expression of activated ER-α and its prognostic
implications in a series of patients with surgically resected stage II-III CRC.
Methods: Phosphorylated ER-α [Ser167] expression was evaluated by
immunohistochemistry (IHC) in tissue microarrays (TMA) of 218 CRC
paraffin-embedded tumor samples. A pER-α score was calculated for each sample
according to staining intensity and proportion of stained cells assessed by two
pathologists blinded to the clinical data. Univariate and multivariate analyses were
performed to assess the correlation of pER-α score with clinicopathological features
and survival.
Results: pER-α staining was negative in 39 tumors (18%), 1+ in 164(75%), 2+ in
11(5%), and unavailable in 4(2%). Half of the samples had positive staining in
>10% of tumor cells. A high pER-α score was more common in women
(female:56% vs male:45%; p = 0.07), older patients (>65years:56% vs 120mg/dl:66% vs
A, overall response rate (partial reponse and stable disease) was 25%
for the patients with the A/A genotype, 73% for the C/A genotype and 85% for C/C
(p = 0.032). Progression free survival (PFS) was 2.5 months for patients harbouring
the A/A genotype compare to 8 months for the patients with A/C and C/C
genotypes (p = 0.0001); overall survival was also superior for patients containing the
allele C genotypes (5 months for AA and 18 months for C/A and C/C); p = 0.001.
For the polymorphism g.75395312G > A, the G/G genotype overall response rate was
100% compare to 69% for the A/G and A/A genotypes (p = 0.048). PFS did not
reach statistical significance for this polymorphism. None of the two Tag SNPs for
the EREG ligand were found to correlate with response.
Conclusions: AREG polimorphisms may help to identify refractory mCRC patients
who will benefit from irinotecan plus anti-EGFR treatment.
Disclosure: All authors have declared no conflicts of interest.
537P DIFFERENCES IN KRAS AND BRAF MUTATION PREVALENCE
IN METASTATIC COLORECTAL CARCINOMA USING
HIGH-SENSITIVITY TAQMELT VS ARMS-SCORPION PCR
ASSAYS
S. Zazo 1 , T. Caldes 2 , N. Pérez González 1 , J. Madoz 1 ,J.Satre 2 , R. Manso 1 ,
D. Ferrandez 3 , T. Ramos 4 , J. Garcia-Foncillas 5 , E. Diaz-Rubio 2
1 Pathology Department, Fundacion Jimenez Diaz, Madrid, SPAIN, 2 Medical
Oncology, Hospital Clinico San Carlos, Madrid, SPAIN, 3 Roche Farma, Roche
Farma Spain, Madrid, SPAIN, 4 Roche Diagnostics, Roche Diagnostics,
Barcelona, SPAIN, 5 Oncology, Fundación Jiménez Díaz, Madrid, SPAIN
Background: Activating KRAS mutations are present in approximately 35-40% of
patients with metastatic colorectal cancer (mCRC) and have been significantly
associated with lack of response to anti-EGFR antibody therapies. Although current
guidelines recommend testing for frequent KRAS codons 12/13 mutations (G12D,
G12A, G12V, G12S, G12R, G12C and G13D), emerging data indicate that additional
KRAS and BRAF mutations might be also predictive of non-responsiveness to
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix183